Objective To investigate the effects of exogenous hydrogen sulfide (H2S) on the mitochondrial function during focal cerebral ischemia and the relationship with mitochondrial damage in rats.Methods Eighty male Sprague-Dawley rats,weighing 250-300 g,were randomly divided into 5 groups (n =16 each):sham operation group (group S),cerebral ischemia group (group CI),and high,medium and low dose NaHS groups (NaHS1,NaHS2 and NaHS3 groups).The animals were anesthetized with intraperitoneal chloral hydrate.The focal cerebral ischemia was induced by middle cerebral artery occlusion.Normal saline 1 ml/kg was injected intraperitoneally at 3 h after the model was established.NaHS 2.8,1.4 and 0.7 mg/kg were injected intraperitoneally in NaHS1,NaHS2 and NaHS3 groups,respectively.At 24 h after the model was established,the cerebral infarct volume was determined.The changes in the cerebral infarct volume were observed after administration of NaHS.Cerebral specimens on the ischemic side were obtained for determination of the content of H2S and activity of 3-mercaptopyruvate sulphurtransferase (3MST) in brain tissues.The mitochondria were extracted for determination of the activity and swelling of mitochondrial membrane and changes in the total ATPase,superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) content.Results Compared with group S,the cerebral infarct volume was significantly enlarged in CI,NaHS1,NaHS2 and NaHS3 groups,the content of H2 S in brain tissues and activity of mitochondrial 3MST were decreased in CI,NaHS2 and NaHS3 groups,the activities of mitochondria,SOD and GSH-Px were significantly decreased,and the swelling of mitochondrial membrane and content of MDA were increased in CI and NaHS3 groups,the total ATPase activity was decreased in CI group,and SOD activity was decreased in NaHS1 and NaHS2 groups.Compared with CI group,the cerebral infarct volume was significantly reduced,the content of H2 S in brain tissues and activity of mitochondrial 3MST were increased,the activities of mitochondria,total ATPase,SOD and GSH-Px were increased,the swelling of mitochondrial membrane was reduced,and the content of MDA was decreased in NaHS1 and NaHS2 groups.Conclusion The mechanism by which exogenous H2 S mitigates focal cerebral ischemia is related to enhanced anti-oxidant activity of mitochondria and reduced mitochondrial damage in rats.

ObjectiveTo evaluate the effect of aminooxyacetic acid on focal cerebral ischemia injury in rats.MethodsEighty healthy male SD rats aged 2.5 month weighing 250-280 g were randomly divided into five groups( n ＝ 16 each):sham operation group(group S),cerebral ischemia group(group Ⅰ),aminooxoacetic acid low,medium and high dose groups(groups AL,AM and AH ).Focal cerebral ischemia was induced by occlusion of middle cerebral artery using a nylon thread with rounding tip which was inserted into right internal carotid artery in groups I,AL,AM and AH.Intraperitoneal amincoxoacetic acid 25,50 and 100 μmol/kg were administered at 3 h of ischemia in groups AL,AM and AH respectively,while equal volume of normal saline 1 ml/kg were injected in groups S and I.Neurological function was assessed and scored (0＝ no deficit,4＝ unable to move,unconscious) in 8 rats at 21 h after aminooxyacetic acid administration in each group.The animals were then sacrificed and the brains were removed for determination of the cystathionine beta-synthase (CBS) activities in cortex,hippocampus and striatum corpora.The other eight rats of each group were sacrificed at 21 h after amincoxoacetic acid administration for determination of the cerebral infarct volume.ResultsCompared with group S,the neurological deficit scores and the CBS activities in cortex and hippocampus were significantly increased,the infarct volumes were significantly enlarged in group Ⅰ ( P < 0.05).Compared with group Ⅰ,the neurological deficit scores and the CBS activities in cortex and hippocampus were significantly decreased,the cerebral infarct volumes were significantly reduced in groups AM and AH (P < 0.05).There was no significant difference in the above-mentioned variables between groups AL and Ⅰ.ConclusionAminooxoacetic acid can reduce focal cerebral ischemia injury by decreasing CBS activity and reducing H2 S production in rats.

Objective To compare the effectiveness and safety of semaglutide with dulaglutide in patients diagnosed with type 2 diabetes.Methods A multicenter retrospective cohort study was conducted to include patients with type 2 diabetes who received semaglutide or dulaglutide treatment at three hospitals between April 2021 and July 2023 in the study.The patients were divided into the semaglutide group(SEMA group)and the dulaglutide group(DULA group)based on their treatment.Propensity score matching was used to pair the two groups in a 1:1 ratio,aligning them based on baseline characteristics such as gender,age,body mass index,blood glucose levels,duration of diabetes,and complications.Various parameters including fasting blood glucose,2-hour postprandial blood glucose,glycosylated hemoglobin(HbA1c),serum creatinine,urea nitrogen levels,estimated glomerular filtration rate(eGFR),urinary albumin/creatinine ratio(UACR),and occurrences of adverse reactions were assessed at 3,6,9,and 12 months after the treatment.Results After propensity score matching,98 patients were included in both the SEMA and DULA groups,showing no statistically significant differences in baseline characteristics between the groups(P＞0.05).At each follow-up point,the fasting blood glucose,2-hour postprandial blood glucose,and HbA1c levels of both groups showed a significant decrease compared to the baseline(P≤0.05).The inter-group comparison revealed no statistically significant differences in the changes in fasting blood glucose,2-hour postprandial blood glucose,and HbA1c levels between the two groups(P＞0.05).At the 6th month,the SEMA group exhibited a statistically significant higher rate of HbA1c＜7％compared to the DULA group(P＜0.05).In the SEMA group,serum creatinine and urea nitrogen decreased significantly at the 6th month compared to baseline,while eGFR showed an increase at the 3rd and 6th month,and UACR decreased,all with statistical significance(P＜0.05).In the DULA group,there was a statistically significant increase in serum creatinine and decrease at the 3rd and 6th months in eGFR,respectively.Additionally,urea nitrogen levels decreased significantly at the 9th month,all differences were statistically significant(P＜0.05).The inter-group comparison revealed that at the 3rd and 6th month,the SEMA group exhibited a greater reduction in serum creatinine levels compared to the DULA group.Additionally,the SEMA group demonstrated a more pronounced increase in eGFR levels than the DULA group,with statistical significance(P＜0.05).At the 6th month,the SEMA group exhibited a significantly greater decrease in UACR and a significantly lower incidence of renal insufficiency compared to the DULA group(P＜0.05).There were no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Semaglutide and dulaglutide can significantly improve blood glucose control,exhibit comparable effectiveness and safety in lowering blood glucose levels,and semaglutide has a potentially protective effect on renal function.